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Publication : Down-regulation of GLT25D1 inhibited collagen secretion and involved in liver fibrogenesis.

First Author  He L Year  2020
Journal  Gene Volume  729
Pages  144233 PubMed ID  31759980
Mgi Jnum  J:283330 Mgi Id  MGI:6385078
Doi  10.1016/j.gene.2019.144233 Citation  He L, et al. (2020) Down-regulation of GLT25D1 inhibited collagen secretion and involved in liver fibrogenesis. Gene 729:144233
abstractText  Collagen beta (1-O) galactosyltransferase 1 (GLT25D1) has been reported to transfer galactose to hydroxylysine residues via beta (1-O) linkages in collagen. However, the role of Glt25d1 in liver fibrogenesis is still unknow. Recently, we generated a Glt25d1 knockout mouse to elucidate the role of Glt25d1 in vivo. However, we found that complete deletion of the Glt25d1 gene resulted in embryonic lethality at E11.5. Histopathological analysis revealed that dysplasia in Glt25d1(-/-) labyrinth with defects of the vascular network. Immunohistochemical showed that the decrease in proliferation of Glt25d1(-/-) liver and the developing central nervous system (CNS). The role of Glt25d1 in liver fibrogenesis was explored by Glt25d1(+/-) mice. Glt25d1(+/-) mice and wild-type (WT) mice were injected intraperitoneally with the same dose of CCl4. The higher level of serum alanine aminotransferase was observed in Glt25d1(+/-) mice. Reverse transcription-quantitative polymerase chainreaction demonstrated that the mRNA expression levels of the inflammatory cytokines such as, Tnf-alpha, Cxcl-1 and Mcp-1, showed a significantly increase in CCl4-treated Glt25d1(+/-) mice. Collagen-I, collagen-III and alpha-SMA transcripts accumulation was markedly increased in the Glt25d1(+/-) mice. However, Masson's trichrome staining revealed a trend to decrease in the ECM proteins deposition of Glt25d1(+/-) liver. Immunohistochemistry and Western blots revealed that the protein expression of Collagen-III was reduced and a trend to a decrease in collagen-I was observed in the Glt25d1(+/-) liver compared with those of WT mice. Our results demonstrate that Glt25d1 knockout results in embryonic lethality and down-regulation of Glt25d1 may inhibit collagen secretion during liver fibrogenesis.
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